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CD4+ T cell–mediated HLA class II cross-restriction in HIV controllers

Galperin, Moran, Farenc, Carine, Mukhopadhyay, Madhura, Jayasinghe, Dhilshan, Decroos, Amandine, Benati, Daniela, Tan, Li Lynn, Ciacchi, Lisa, Reid, Hugh H., Rossjohn, Jamie, Chakrabarti, Lisa A. and Gras, Stephanie 2018. CD4+ T cell–mediated HLA class II cross-restriction in HIV controllers. Science Immunology 3 (24) , eaat0687. 10.1126/sciimmunol.aat0687

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Rare individuals, termed HIV controllers, spontaneously control HIV infection by mounting efficient T cell responses against the virus. Protective CD4+ T cell responses from HIV controllers involve high-affinity public T cell receptors (TCRs) recognizing an immunodominant capsid epitope (Gag293) presented by a remarkably broad array of human leukocyte antigen (HLA) class II molecules. Here, we determine the structures of a prototypical public TCR bound to HLA-DR1, HLA-DR11, and HLA-DR15 molecules presenting the Gag293 epitope. TCR recognition was driven by contacts with the Gag293 epitope, a feature that underpinned the extensive HLA cross-restriction. These high-affinity TCRs promoted mature immunological synapse formation and cytotoxic capacity in both CD4+ and CD8+ T cells. The public TCRs suppressed HIV replication in multiple genetic backgrounds ex vivo, emphasizing the functional advantage conferred by broad HLA class II cross-restriction.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association for the Advancement of Science
ISSN: 2470-9468
Date of First Compliant Deposit: 30 July 2018
Date of Acceptance: 18 April 2018
Last Modified: 20 Jan 2021 16:18

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